{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:30:24Z","timestamp":1792017024534,"version":"4.4.0"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Infection with the hepatitis B virus (HBV) continues to pose a major threat to public health as approximately 292 million people worldwide are currently living with the chronic form of the disease, for which treatment is non-curative. Chronic HBV infections often progress to hepatocellular carcinoma (HCC) which is one of the world\u2019s leading causes of cancer-related deaths. Although the process of hepatocarcinogenesis is multifaceted and has yet to be fully elucidated, several studies have implicated numerous long non-coding RNAs (lncRNAs) as contributors to the development of HCC. These host-derived lncRNAs, which are often dysregulated as a consequence of viral infection, have been shown to function as signals, decoys, guides, or scaffolds, to modulate gene expression at epigenetic, transcriptional, post-transcriptional and even post-translational levels. These lncRNAs mainly function to promote HBV replication and oncogene expression or downregulate tumor suppressors. Very few lncRNAs are known to suppress tumorigenesis and these are often downregulated in HCC. In this review, we describe the mechanisms by which lncRNA dysregulation in HBV-related HCC promotes tumorigenesis and cancer progression.<\/jats:p>","DOI":"10.3389\/fimmu.2022.834650","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T05:09:30Z","timestamp":1643346570000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Diversity of Dysregulated Long Non-Coding RNAs in HBV-Related Hepatocellular Carcinoma"],"prefix":"10.3389","volume":"13","author":[{"given":"Nazia","family":"Samudh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Creanne","family":"Shrilall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Arbuthnot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristie","family":"Bloom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Ely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5405","article-title":"Long Non-Coding RNAs in Development and Disease: Conservation to Mechanisms","volume":"250","author":"Tsagakis","year":"2020","journal-title":"J Pathol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0184-5","article-title":"Regulation of Gene Expression by Cis-Acting Long non-Coding RNAs","volume":"21","author":"Gil","year":"2020","journal-title":"Nat Rev Genet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13133115","article-title":"The lncRNAs in HBV-Related HCCs: Targeting Chromatin Dynamics and Beyond","volume":"13","author":"Alfano","year":"2021","journal-title":"Cancers"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2015.07.025","article-title":"The Role of Long Non-Coding RNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma","volume":"212","author":"Moyo","year":"2016","journal-title":"Virus Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4770","article-title":"LncRNAs and Cancer","volume":"12","author":"Zhang","year":"2016","journal-title":"Oncol Lett"},{"key":"B6","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1146\/annurev.iy.13.040195.000333","article-title":"Hepatitis B Virus Immunopathogenesis","volume":"13","author":"Chisari","year":"1995","journal-title":"Annu Rev Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24563","article-title":"Long Noncoding RNA High Expression in Hepatocellular Carcinoma Facilitates Tumor Growth Through Enhancer of Zeste Homolog 2 in Humans","volume":"54","author":"Yang","year":"2011","journal-title":"Hepatol Baltim Md"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/srep23521","article-title":"HBx-Upregulated lncRNA UCA1 Promotes Cell Growth and Tumorigenesis by Recruiting EZH2 and Repressing p27Kip1\/CDK2 Signaling","volume":"6","author":"Hu","year":"2016","journal-title":"Sci Rep"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.03.031","article-title":"Linc00152 Promotes Cancer Progression in Hepatitis B Virus-Associated Hepatocellular Carcinoma","volume":"90","author":"Deng","year":"2017","journal-title":"Biomed Pharmacother"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5970","article-title":"LINC00152 Promotes Proliferation in Hepatocellular Carcinoma by Targeting EpCAM via the mTOR Signaling Pathway","volume":"6","author":"Ji","year":"2015","journal-title":"Oncotarget"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3892\/or.2019.7444","article-title":"lncRNA PVT1 Promotes Hepatitis B Virus\u2212Positive Liver Cancer Progression by Disturbing Histone Methylation on the C\u2212Myc Promoter","volume":"43","author":"Jiang","year":"2019","journal-title":"Oncol Rep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-319637","article-title":"Hepatitis B Protein HBx Binds the DLEU2 lncRNA to Sustain cccDNA and Host Cancer-Related Gene Transcription","volume":"69","author":"Salerno","year":"2020","journal-title":"Gut"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31284","article-title":"Hepatitis B Virus DNA Polymerase Restrains Viral Replication Through the CREB1\/HOXA Distal Transcript Antisense RNA Homeobox A13 Axis","volume":"73","author":"Zhao","year":"2021","journal-title":"Hepatology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-2928","article-title":"PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 During Hepatitis B Virus-Induced Liver Carcinogenesis","volume":"75","author":"Zhang","year":"2015","journal-title":"Cancer Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28698","article-title":"RNA Helicase DEAD Box Protein 5 Regulates Polycomb Repressive Complex 2\/Hox Transcript Antisense Intergenic RNA Function in Hepatitis B Virus Infection and Hepatocarcinogenesis","volume":"64","author":"Zhang","year":"2016","journal-title":"Hepatol Baltim Md"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1042\/CS20200970","article-title":"LncRNA HOTAIR Modulates Hepatitis B Virus Transcription and Replication by Enhancing SP1 Transcription Factor","volume":"134","author":"Ren","year":"2020","journal-title":"Clin Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.04.008","article-title":"Long Non-Coding RNA HULC Activates HBV by Modulating HBx\/STAT3\/miR-539\/APOBEC3B Signaling in HBV-Related Hepatocellular Carcinoma","volume":"454","author":"Liu","year":"2019","journal-title":"Cancer Lett"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.342113","article-title":"Elevation of Highly Up-Regulated in Liver Cancer (HULC) by Hepatitis B Virus X Protein Promotes Hepatoma Cell Proliferation via Down-Regulating P18","volume":"287","author":"Du","year":"2012","journal-title":"J Biol Chem"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq285","article-title":"CREB Up-Regulates Long non-Coding RNA, HULC Expression Through Interaction With microRNA-372 in Liver Cancer","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.572693","article-title":"Activation of LTBP3 Gene by a Long Noncoding RNA (lncRNA) MALAT1 Transcript in Mesenchymal Stem Cells From Multiple Myeloma","volume":"289","author":"Li","year":"2014","journal-title":"J Biol Chem"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101652","article-title":"Upregulation of IL-23 Expression in Patients With Chronic Hepatitis B Is Mediated by the HBx\/ERK\/NF-\u03bab Pathway","volume":"188","author":"Xia","year":"2012","journal-title":"J Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108877","article-title":"HBx-Related Long Non-Coding RNA 01152 Promotes Cell Proliferation and Survival by IL-23 in Hepatocellular Carcinoma","volume":"115","author":"Chen","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"B23","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1186\/s12985-017-0903-5","article-title":"Hepatitis B Virus X Protein Induces Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Regulating Long Non-Coding RNA","volume":"14","author":"Jin","year":"2017","journal-title":"Virol J"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.01.030","article-title":"Viral-Human Chimeric Transcript Predisposes Risk to Liver Cancer Development and Progression","volume":"25","author":"Lau","year":"2014","journal-title":"Cancer Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.09.013","article-title":"Hepatitis B Virus-Human Chimeric Transcript HBx-LINE1 Promotes Hepatic Injury via Sequestering Cellular microRNA-122","volume":"64","author":"Liang","year":"2016","journal-title":"J Hepatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5667","article-title":"HBx-Related Long Non-Coding RNA DBH-AS1 Promotes Cell Proliferation and Survival by Activating MAPK Signaling in Hepatocellular Carcinoma","volume":"6","author":"Huang","year":"2015","journal-title":"Oncotarget"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.08.079","article-title":"LncRNA DBH-AS1 Facilitates the Tumorigenesis of Hepatocellular Carcinoma by Targeting miR-138 via FAK\/Src\/ERK Pathway","volume":"107","author":"Bao","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.7150\/thno.34273","article-title":"LncRNA PCNAP1 Modulates Hepatitis B Virus Replication and Enhances Tumor Growth of Liver Cancer","volume":"9","author":"Feng","year":"2019","journal-title":"Theranostics"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6627173","article-title":"LncRNA PCNAP1 Promotes Hepatoma Cell Proliferation Through Targeting miR-340-5p and Is Associated With Patient Survival","volume":"2021","author":"He","year":"2021","journal-title":"J Oncol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.bbrc.2018.11.091","article-title":"Hepatitis B Virus X Protein Related lncRNA WEE2-AS1 Promotes Hepatocellular Carcinoma Proliferation and Invasion","volume":"508","author":"Hu","year":"2019","journal-title":"Biochem Biophys Res Commun"},{"key":"B31","doi-asserted-by":"publisher","first-page":"591","DOI":"10.3727\/096504020X15982623243955","article-title":"Long Noncoding RNA WEE2-AS1 Plays an Oncogenic Role in Glioblastoma by Functioning as a Molecular Sponge for MicroRNA-520f-3p","volume":"28","author":"Lin","year":"2021","journal-title":"Oncol Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.08.029","article-title":"Long Non-Coding RNA Unigene56159 Promotes Epithelial-Mesenchymal Transition by Acting as a ceRNA of miR-140-5p in Hepatocellular Carcinoma Cells","volume":"382","author":"Lv","year":"2016","journal-title":"Cancer Lett"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.528026","article-title":"Differential Role of Snail1 and Snail2 Zinc Fingers in E-Cadherin Repression and Epithelial to Mesenchymal Transition*","volume":"289","author":"Villarejo","year":"2014","journal-title":"J Biol Chem"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_201906_18208","article-title":"LncRNA H19 Promotes the Development of Hepatitis B Related Hepatocellular Carcinoma Through Regulating microRNA-22 via EMT Pathway","volume":"23","author":"Li","year":"2019","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.molimm.2019.09.006","article-title":"LncRNA H19\/microRNA-675\/Ppar\u03b1 Axis Regulates Liver Cell Injury and Energy Metabolism Remodelling Induced by Hepatitis B X Protein via Akt\/mTOR Signalling","volume":"116","author":"Liu","year":"2019","journal-title":"Mol Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgs381","article-title":"Epigenetic Activation of the MiR-200 Family Contributes to H19-Mediated Metastasis Suppression in Hepatocellular Carcinoma","volume":"34","author":"Zhang","year":"2013","journal-title":"Carcinogenesis"},{"key":"B37","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.canlet.2018.05.010","article-title":"LncRNA N335586\/miR-924\/CKMT1A Axis Contributes to Cell Migration and Invasion in Hepatocellular Carcinoma Cells","volume":"429","author":"Fan","year":"2018","journal-title":"Cancer Lett"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26195","article-title":"Hepatitis B Virus X Protein (HBx)-Related Long Noncoding RNA (lncRNA) Down-Regulated Expression by HBx (Dreh) Inhibits Hepatocellular Carcinoma Metastasis by Targeting the Intermediate Filament Protein Vimentin","volume":"57","author":"Huang","year":"2013","journal-title":"Hepatol Baltim Md"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6436","article-title":"Downregulated Long non-Coding RNA DREH Promotes Cell Proliferation in Hepatitis B Virus-Associated Hepatocellular Carcinoma","volume":"14","author":"Lv","year":"2017","journal-title":"Oncol Lett"},{"key":"B40","doi-asserted-by":"publisher","first-page":"11593","DOI":"10.1038\/s41598-019-48116-1","article-title":"LncRNA SAMD12-AS1 Promotes Cell Proliferation and Inhibits Apoptosis by Interacting With NPM1","volume":"9","author":"Liu","year":"2019","journal-title":"Sci Rep"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30098","article-title":"Hepatitis B Virus-Upregulated LNC-HUR1 Promotes Cell Proliferation and Tumorigenesis by Blocking P53 Activity","volume":"68","author":"Liu","year":"2018","journal-title":"Hepatol Baltim Md"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25895","article-title":"Long Noncoding RNA Associated With Microvascular Invasion in Hepatocellular Carcinoma Promotes Angiogenesis and Serves as a Predictor for Hepatocellular Carcinoma Patients\u2019 Poor Recurrence-Free Survival After Hepatectomy","volume":"56","author":"Yuan","year":"2012","journal-title":"Hepatol Baltim Md"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41419-018-1231-4","article-title":"A Novel lncRNA, TCONS_00006195, Represses Hepatocellular Carcinoma Progression by Inhibiting Enzymatic Activity of ENO1","volume":"9","author":"Yu","year":"2018","journal-title":"Cell Death Dis"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8129","article-title":"Ftx Non Coding RNA-Derived miR-545 Promotes Cell Proliferation by Targeting RIG-I in Hepatocellular Carcinoma","volume":"7","author":"Liu","year":"2016","journal-title":"Oncotarget"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109782","article-title":"The miR-545\/374a Cluster Encoded in the Ftx lncRNA Is Overexpressed in HBV-Related Hepatocellular Carcinoma and Promotes Tumorigenesis and Tumor Progression","volume":"9","author":"Zhao","year":"2014","journal-title":"PloS One"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.17305\/bjbms.2018.2800","article-title":"Analysis of Long Non-Coding RNA (lncRNA) Expression in Hepatitis B Patients","volume":"18","author":"Susluer","year":"2018","journal-title":"Bosn J Basic Med Sci"},{"key":"B47","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1186\/s12967-016-1085-4","article-title":"Analysis of Long Noncoding RNA Expression in Hepatocellular Carcinoma of Different Viral Etiology","volume":"14","author":"Zhang","year":"2016","journal-title":"J Transl Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-020-00915-4","article-title":"Transcriptomic Profiling of Long Non-Coding RNAs in Non-Virus Associated Hepatocellular Carcinoma","volume":"78","author":"Liu","year":"2020","journal-title":"Cell Biochem Biophys"},{"key":"B49","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3390\/ncrna4030019","article-title":"Long Non-Coding RNAs in Obesity-Induced Cancer","volume":"4","author":"Yau","year":"2018","journal-title":"Non-Coding RNA"},{"key":"B50","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12986-021-00552-5","article-title":"A Comprehensive Review of Long Non-Coding RNAs in the Pathogenesis and Development of non-Alcoholic Fatty Liver Disease","volume":"18","author":"Shabgah","year":"2021","journal-title":"Nutr Metab"},{"key":"B51","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3892\/ijo.2019.4909","article-title":"Long Non\u2212Coding RNAs in HBV\u2212Related Hepatocellular Carcinoma (Review)","volume":"56","author":"Zhang","year":"2019","journal-title":"Int J Oncol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks296","article-title":"Emerging Functional and Mechanistic Paradigms of Mammalian Long non-Coding RNAs","volume":"40","author":"Moran","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.08.018","article-title":"Molecular Mechanisms of Long Noncoding RNAs","volume":"43","author":"Wang","year":"2011","journal-title":"Mol Cell"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904715106","article-title":"Many Human Large Intergenic Noncoding RNAs Associate With Chromatin-Modifying Complexes and Affect Gene Expression","volume":"106","author":"Khalil","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.7","article-title":"Structure of the PRC2 Complex and Application to Drug Discovery","volume":"38","author":"Shi","year":"2017","journal-title":"Acta Pharmacol Sin"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1101\/gad.381706","article-title":"Genome-Wide Mapping of Polycomb Target Genes Unravels Their Roles in Cell Fate Transitions","volume":"20","author":"Bracken","year":"2006","journal-title":"Genes Dev"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/9187316","article-title":"The Interaction of lncRNA-HEIH and lncRNA-HULC With HBXIP in Hepatitis B Patients","volume":"2018","author":"Ruan","year":"2018","journal-title":"Gastroenterol Res Pract"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0134","article-title":"Rapid Identification of UCA1 as a Very Sensitive and Specific Unique Marker for Human Bladder Carcinoma","volume":"12","author":"Wang","year":"2006","journal-title":"Clin Cancer Res"},{"key":"B59","doi-asserted-by":"publisher","first-page":"E1118","DOI":"10.3390\/cells8101118","article-title":"The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges","volume":"8","author":"Loh","year":"2019","journal-title":"Cells"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.12.004","article-title":"EpCAM-Positive Hepatocellular Carcinoma Cells Are Tumor-Initiating Cells With Stem\/Progenitor Cell Features","volume":"136","author":"Yamashita","year":"2009","journal-title":"Gastroenterology"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27239","article-title":"Oncofetal Long Noncoding RNA PVT1 Promotes Proliferation and Stem Cell-Like Property of Hepatocellular Carcinoma Cells by Stabilizing NOP2: WANG ET AL","volume":"60","author":"Wang","year":"2014","journal-title":"Hepatology"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20046","article-title":"DLEU2 Encodes an Antisense RNA for the Putative Bicistronic RFP2\/LEU5 Gene in Humans and Mouse: Antisense Relationship Between DLEU2 and RFP2\/LEU5. Genes","volume":"40","author":"Corcoran","year":"2004","journal-title":"Chromosomes Cancer"},{"key":"B63","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.ccr.2009.11.019","article-title":"The DLEU2\/miR-15a\/16-1 Cluster Controls B Cell Proliferation and Its Deletion Leads to Chronic Lymphocytic Leukemia","volume":"17","author":"Klein","year":"2010","journal-title":"Cancer Cell"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/nature09819","article-title":"A Long Noncoding RNA Maintains Active Chromatin to Coordinate Homeotic Gene Expression","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.691766","article-title":"The Functions of Hepatitis B Virus Encoding Proteins: Viral Persistence and Liver Pathogenesis","volume":"12","author":"Zhao","year":"2021","journal-title":"Front Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S315716","article-title":"Exosomal lncRNA HOTTIP Mediates Antiviral Effect of Tenofovir Alafenamide (TAF) on HBV Infection","volume":"14","author":"Liu","year":"2021","journal-title":"J Inflamm Res Volume"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26740","article-title":"Long Noncoding RNA HOTTIP\/HOXA13 Expression is Associated With Disease Progression and Predicts Outcome in Hepatocellular Carcinoma Patients","volume":"59","author":"Quagliata","year":"2014","journal-title":"Hepatology"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.21037\/hbsn.2018.10.07","article-title":"Long Noncoding RNA HOTTIP Expression Predicts Tumor Recurrence in Hepatocellular Carcinoma Patients Following Liver Transplantation","volume":"7","author":"Wu","year":"2018","journal-title":"Hepatobiliary Surg Nutr"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.022","article-title":"Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs","volume":"129","author":"Rinn","year":"2007","journal-title":"Cell"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1126\/science.1192002","article-title":"Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes","volume":"329","author":"Tsai","year":"2010","journal-title":"Science"},{"key":"B71","doi-asserted-by":"publisher","first-page":"e3255","DOI":"10.1371\/journal.pone.0003255","article-title":"ZNF198 Stabilizes the LSD1-CoREST-HDAC1 Complex on Chromatin Through its MYM-Type Zinc Fingers","volume":"3","author":"Gocke","year":"2008","journal-title":"PloS One"},{"key":"B72","doi-asserted-by":"publisher","first-page":"4268","DOI":"10.1038\/s41467-018-06739-4","article-title":"Tridimensional Infiltration of DNA Viruses Into the Host Genome Shows Preferential Contact With Active Chromatin","volume":"9","author":"Moreau","year":"2018","journal-title":"Nat Commun"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.7150\/thno.49629","article-title":"Restoration of RNA Helicase DDX5 Suppresses Hepatitis B Virus (HBV) Biosynthesis and Wnt Signaling in HBV-Related Hepatocellular Carcinoma","volume":"10","author":"Mani","year":"2020","journal-title":"Theranostics"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.093963","article-title":"Polo-Like Kinase 1 Activated by the Hepatitis B Virus X Protein Attenuates Both the DNA Damage Checkpoint and DNA Repair Resulting in Partial Polyploidy","volume":"285","author":"Studach","year":"2010","journal-title":"J Biol Chem"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.08.026","article-title":"Characterization of HULC, a Novel Gene With Striking Up-Regulation in Hepatocellular Carcinoma, as Noncoding RNA","volume":"132","author":"Panzitt","year":"2007","journal-title":"Gastroenterology"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.9.3819","article-title":"The Hepatitis B Virus X Protein Targets the Basic Region-Leucine Zipper Domain of CREB","volume":"92","author":"Williams","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243462","article-title":"Specific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus cccDNA","volume":"343","author":"Lucifora","year":"2014","journal-title":"Science"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.054","article-title":"The Haploinsufficient Tumor Suppressor P18 Upregulates P53 via Interactions With ATM\/ATR","volume":"120","author":"Park","year":"2005","journal-title":"Cell"},{"key":"B79","article-title":"HBx-Related Long non-Coding RNA MALAT1 Promotes Cell Metastasis via Up-Regulating LTBP3 in Hepatocellular Carcinoma","volume":"7","author":"Hou","year":"2017","journal-title":"Am J Cancer Res"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.012","article-title":"3\u2019 End Processing of a Long Nuclear-Retained Noncoding RNA Yields a tRNA-Like Cytoplasmic RNA","volume":"135","author":"Wilusz","year":"2008","journal-title":"Cell"},{"key":"B81","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/s41420-021-00497-x","article-title":"mascRNA and its Parent lncRNA MALAT1 Promote Proliferation and Metastasis of Hepatocellular Carcinoma Cells by Activating ERK\/MAPK Signaling Pathway","volume":"7","author":"Xie","year":"2021","journal-title":"Cell Death Discovery"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb08049.x","article-title":"A Role of the Latent TGF-Beta 1-Binding Protein in the Assembly and Secretion of TGF-Beta 1","volume":"10","author":"Miyazono","year":"1991","journal-title":"EMBO J"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-017-0075-1","article-title":"LTBP3 Promotes Early Metastatic Events During Cancer Cell Dissemination","volume":"37","author":"Deryugina","year":"2018","journal-title":"Oncogene"},{"key":"B84","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.jcmgh.2020.04.018","article-title":"Alternative Splicing in Hepatocellular Carcinoma","volume":"10","author":"Lee","year":"2020","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01600-w","article-title":"Long non-Coding RNAs are Involved in Alternative Splicing and Promote Cancer Progression","author":"Ouyang","year":"2021","journal-title":"Br J Cancer"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1101\/gad.455708","article-title":"A Natural Antisense Transcript Regulates Zeb2\/Sip1 Gene Expression During Snail1-Induced Epithelial-Mesenchymal Transition","volume":"22","author":"Beltran","year":"2008","journal-title":"Genes Dev"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00260-X","article-title":"The Two-Handed E Box Binding Zinc Finger Protein SIP1 Downregulates E-Cadherin and Induces Invasion","volume":"7","author":"Comijn","year":"2001","journal-title":"Mol Cell"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.07.014","article-title":"A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language","volume":"146","author":"Leonardo","year":"2011","journal-title":"Cell"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004449200","article-title":"Hepatitis B Viral Transactivator HBx Alleviates P53-Mediated Repression of \u03b1-Fetoprotein Gene Expression","volume":"275","author":"Ogden","year":"2000","journal-title":"J Biol Chem"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-5-87","article-title":"The PCNA Pseudogenes in the Human Genome","volume":"5","author":"Stoimenov","year":"2012","journal-title":"BMC Res Notes"},{"key":"B91","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1128\/mcb.10.1.28-36.1990","article-title":"The Product of the H19 Gene may Function as an RNA","volume":"10","author":"Brannan","year":"1990","journal-title":"Mol Cell Biol"},{"key":"B92","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1136\/mp.50.1.34","article-title":"The Product of the Imprinted H19 Gene is an Oncofetal RNA","volume":"50","author":"Ariel","year":"1997","journal-title":"Mol Pathol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-0037","article-title":"The C-Myc Oncogene Directly Induces the H19 Noncoding RNA by Allele-Specific Binding to Potentiate Tumorigenesis","volume":"66","author":"Barsyte-Lovejoy","year":"2006","journal-title":"Cancer Res"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.2741\/4608","article-title":"Expression and Role of Long non-Coding RNA H19 in Carcinogenesis","volume":"23","author":"Ishiwata","year":"2018","journal-title":"Front Biosci"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S186561","article-title":"Integrated Analysis of lncRNA-Associated ceRNA Network Reveals Potential Biomarkers for the Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma","volume":"11","author":"Li","year":"2019","journal-title":"Cancer Manage Res"},{"key":"B96","article-title":"BC-819, a Plasmid Comprising the H19 Gene Regulatory Sequences and Diphtheria Toxin A, for the Potential Targeted Therapy of Cancers","volume":"12","author":"Smaldone","year":"2010","journal-title":"Curr Opin Mol Ther"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(04)00110-2","article-title":"Nucleolar Protein NPM Interacts With HDM2 and Protects Tumor Suppressor Protein P53 From HDM2-Mediated Degradation","volume":"5","author":"Kurki","year":"2004","journal-title":"Cancer Cell"},{"key":"B98","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1101\/gr.152902","article-title":"Comparative Sequence Analysis of the X-Inactivation Center Region in Mouse, Human, and Bovine","volume":"12","author":"Chureau","year":"2002","journal-title":"Genome Res"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2011.07.009","article-title":"Origin and Evolution of the Long non-Coding Genes in the X-Inactivation Center","volume":"93","author":"Romito","year":"2011","journal-title":"Biochimie Coding Non-coding: need they be exclusive?"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1261\/rna.351707","article-title":"The Imprinted H19 Noncoding RNA is a Primary microRNA Precursor","volume":"13","author":"Cai","year":"2007","journal-title":"RNA"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1011098108","article-title":"Expression and Functional Role of a Transcribed Noncoding RNA With an Ultraconserved Element in Hepatocellular Carcinoma","volume":"108","author":"Braconi","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2018.03.004","article-title":"Functional Modulation of Gene Expression by Ultraconserved Long Non-Coding RNA TUC338 During Growth of Human Hepatocellular Carcinoma","volume":"2","author":"Wen","year":"2018","journal-title":"iScience"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i23.7208","article-title":"Long Noncoding RNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma","volume":"21","author":"Yu","year":"2015","journal-title":"World J Gastroenterol"},{"key":"B104","article-title":"High Expression of Long non-Coding RNA ANRIL is Associated With Poor Prognosis in Hepatocellular Carcinoma","volume":"8","author":"Hua","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"B105","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13045-015-0146-0","article-title":"Long non-Coding RNA ANRIL is Upregulated in Hepatocellular Carcinoma and Regulates Cell Apoptosis by Epigenetic Silencing of KLF2","volume":"8","author":"Huang","year":"2015","journal-title":"J Hematol Oncol.J Hematol Oncol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.5582\/bst.2016.01140","article-title":"Preliminary Investigation of Five Novel Long non-Coding RNAs in Hepatocellular Carcinoma Cell Lines","volume":"10","author":"Xia","year":"2016","journal-title":"Biosci Trends"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-014-2951-4","article-title":"Investigation of Serum lncRNA-Uc003wbd and lncRNA-AF085935 Expression Profile in Patients With Hepatocellular Carcinoma and HBV","volume":"36","author":"Lu","year":"2015","journal-title":"Tumour Biol J Int Soc Oncodevelopmental Biol Med"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144934","article-title":"Serum LncRNAs Profiles Serve as Novel Potential Biomarkers for the Diagnosis of HBV-Positive Hepatocellular Carcinoma","volume":"10","author":"Wang","year":"2015","journal-title":"PloS One"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1007\/s11262-018-1564-1","article-title":"The Expression and Role of lncRNA AX800134 in Hepatitis B Virus-Related Hepatocellular Carcinoma","volume":"54","author":"Zuo","year":"2018","journal-title":"Virus Genes"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9880","article-title":"Comprehensive Analysis of Long non-Coding RNA Expression Profiles in Hepatitis B Virus-Related Hepatocellular Carcinoma","volume":"7","author":"Gong","year":"2016","journal-title":"Oncotarget"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8765461","article-title":"Identification of a Novel Eight-lncRNA Prognostic Signature for HBV-HCC and Analysis of Their Functions Based on Coexpression and ceRNA Networks","volume":"2020","author":"Zhao","year":"2020","journal-title":"BioMed Res Int"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1007\/s13577-021-00607-y","article-title":"Construction of a ceRNA Network and a Genomic-Clinicopathologic Nomogram to Predict Survival for HBV-Related HCC","volume":"34","author":"Huang","year":"2021","journal-title":"Hum Cell"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i2.220","article-title":"Six-Long non-Coding RNA Signature Predicts Recurrence-Free Survival in Hepatocellular Carcinoma","volume":"25","author":"Gu","year":"2019","journal-title":"World J Gastroenterol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.18897","article-title":"Transcriptomic Profiling of Long non-Coding RNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma","volume":"8","author":"Fan","year":"2017","journal-title":"Oncotarget"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.834650\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T05:09:36Z","timestamp":1643346576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.834650\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":114,"alternative-id":["10.3389\/fimmu.2022.834650"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.834650","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]},"article-number":"834650"}}